Studies on Testosterone Metabolism

Testosterone glucuronide (unlabeled and labeled) was synthesized and injected into three normal men, one pregnant woman, and one child. In addition to testosterone glucuronide itself, several urinary metabolites were isolated. Only 5&androstane steroids were obtained. More 5/!Landrostane-3or, 17/3-diol than Sfl-androsterone was found. Meanwhile, a testosterone tracer gave Sa-metabolites, and more S/3-androsterone than S/3-androstan-3a!,l7fi-diol. These findings provide evidence for a further metabolism of testosterone glucuronide through a selective S&metabolism. A direct metabolism of the conjugate giving 5/?metabolites could be postulated; a metabolic cleavage of testosterone glucuronide seems unlikely, unless it occurred in an undefined organ in which testosterone does not give Sa-compounds. In any case, the glucuronic acid moiety greatly changes the metabolism of testosterone. Calculations made from the specific activity of urinary testosterone after injection of radioactive testosterone and testosterone glucuronide show a production of approximately 5 % of testosterone glucuronide from testosterone in the body. During these studies, the structure of urinary testosterone glucuronide has been observed to be mostly 17fl-yl-p-~glucopyranuronoside, less than 10% (if any) of urinary testosterone glucuronide being possibly 3-enol or diglucuronide or both.